Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study / 中华医学杂志(英文版)

Background@#Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated.@*Methods@#A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation.@*Results@#In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively.@*Conclusions@#R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.@*Trial Registration@#ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.

Effect of Feitai Capsule () on quality of life and progression-free survival of patients with unresectable non-small cell lung cancer / 中国结合医学杂志

<p><b>OBJECTIVE</b>To examine the effect of a Chinese medicinal herbal formula (Feitai Capsule, ) on the quality of life (QOL) and progression-free survival (PFS) of patients with unresectable non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Sixty-two patients were randomly divided into the treatment group (31 cases) and the control group (31 cases). For the treatment group, 4 capsules (1.2 g/capsule) of Feitai Capsule were administered 3 times a day after meals for 3 weeks; then no drug was administered for 1 week. This schedule was continued for at least 3 more cycles (12 weeks totally). If there were no obvious toxic reactions, the treatment was extended. The patients were evaluated at least once every 8 weeks until progressive disease (PD). For the control group, the regular follow-up and evaluation were performed at least once every 8 weeks until PD. Clinical symptoms, objective response, physical constitution and energy, QOL, and PFS were evaluated regularly. Analysis of variance (ANOVA), a non-parametric test, and analysis of covariance were used to compare clinical features, amelioration of clinical symptoms, physical constitution and energy, and QOL. Kaplan-Meier analysis was used to compare the two-group PFS.</p><p><b>RESULTS</b>Sixty patients finished the final evaluation, with 30 patients in each group. Baseline characters between groups were not significantly different (P>0.05). The control group had a 36.7% improvement in clinical symptoms, while the treatment group had a 73.3% improvement. This difference was statistically significant (Z= -2.632, P=0.008). The control group had a 26.7% improvement in the Karnofsky performance status (KPS), while the treatment group had a 53.4% improvement. This was also significantly different (Z=-2.182, P=0.029). A comparative analysis indicated a positive correlation (r=0.917, P<0.001). Compared with the control group, QOL in the treatment group was significantly improved, except in the social/family condition and doctor-patient relationship indicators. The PFS of the treatment group and control group were 6.23 months and 4.67 months, respectively (P=0.048).</p><p><b>CONCLUSION</b>Feitai Capsule, a Chinese medicinal herbal treatment could improve the QOL and extend the PFS of the unresectable NSCLC patients.</p>

Gemcitabine combined with capecitabine in the treatment for 41 patients with relapsed or metastatic biliary tract carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of the combination of gemcitabine with capecitabine in the chemotherapy for patients with relapsed or metastatic biliary tract carcinoma.</p><p><b>METHODS</b>Forty-one patients with unresectable relapsed or metastatic carcinoma of the biliary tract were treated from March 2000 to December 2004. The regimen consisted of intravenous administration of gemcitabine plus oral intake of capecitabine every 3 weeks for more than 2 cycles. The parameters including tumor response, clinical benefit rate,survival and safety were observed.</p><p><b>RESULTS</b>Thirty-six patients were valuable and 5 patients were excluded from this series due to various reasons. Eleven patients (30.1%) had a partial response and another 11 patients (30.1%) experieced stable disease with a clinical benefit rates of 61.1%. The median overall survival time and time to progression were 10 months and 6 months, respectively. The one-year survival rate was 40.0%. The adverse events including nausea, diarrhea and hand-foot syndrome, fatigue, neutropenia, thrombocytopenia were frequently observed, which were usually in grade I or II, rarely in grade III and none in grade IV (NCI-CTC).</p><p><b>CONCLUSION</b>Our results show that the regimen of gemcitabine combined with capecitabine is effective and well tolerated in patients with unresectable relapsed or metastatic carcinoma of the biliary tract.</p>

Study on the relationship between vascular endothelial growth factor and syndrome type of traditional Chinese medicine in patients with gastric carcinoma / 中国中西医结合杂志

<p><b>OBJECTIVE</b>By detecting the expression of vascular endothelial growth factor (VEGF) in different syndrome types of traditional Chinese medicine (TCM) in patients with gastric carcinoma (GC) to investigate the correlation of VEGF and TCM syndrome type for exploring the internal relationship between disease and syndrome.</p><p><b>METHODS</b>The correlated clinical manifestations were recorded in detail and patient's syndrome type was differentiated at beside before operation. After operation, pathological examination on the resected specimen was performed routinely. The expression of VEGF in 104 GC patients of three different syndrome types, i.e. Pi-Wei asthenia type (type 1), Gan-Wei disharmony type (type 2) and phlegm-stasis-poisons stagnant type (type 3)and in 30 patients with superficial gastritis (for control) were determined by immunohistochemical method. The expressions of VEGF in different syndrome types were analyzed by combining with correlated clinical pathological characteristics.</p><p><b>RESULTS</b>(1) The VEGF protein positive expression rate in GC patients was 81.7% (85/104), it was significantly higher than that in the control group with positive rate being zero (P < 0.01). (2) The intensity of VEGF expression was positively correlated with the depth of tumor infiltration, the extent of lymph node metastasis and the pathological staging of cancer (P < 0.01), and showed no evident correlation with the size of tumor and its degree of cell differentiation (P > 0.05). (3) Levels of VEGF expression in various syndrome types were significantly different (P < 0.01), the highest expression showed in the type 3, the second in the type 2, and the lowest in the type 1, comparison between them all showed significant difference (P < 0.01 for 3 vs 1, P < 0.05 for 3 vs 2 and 2 vs 1).</p><p><b>CONCLUSION</b>(1) VEGF could be taken as an index for evaluating the infiltration, metastasis and prognosis of GC. (2) The different expressions of VEGF play different roles in the GC metastatic process of patients of different syndrome types, and the pathogenesis of GC metastasis may be probably various in different syndrome types. VEGF is the relevant gene of GC of type 2 and type 3. (3) High VEGF expression shows positive correlation with the GC metastasis of type 2 and 3, suggesting that the higher the intensity of evil excess, the more possibilities of tumor infiltration and metastasis and the worse the prognoses will be.</p>

Clinical study on treatment of primary hepatocellular carcinoma by Shenqi mixture combined with microwave coagulation / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the short-term efficacy and safety of Shenqi mixture (SQM) combined with microwave coagulation in treating primary hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Seventy-two patients with primary HCC of stage II-III, Karnofsky scoring > or = 50 scores and predicted survival period > or = 3 months were selected and randomly assigned into two groups, the treated group and the control group, 36 in each. Microwave therapy was applied to both groups by double leads, 60 W, 800 sec once a week for two weeks. To the treated group, SQM was given additionally through oral intake of 20 ml, three times a day for 1 month. The changes in tumor size, main symptoms, serum level of alpha-fetoprotein (AFP), immune function and adverse reaction were observed after treatment and the immune parameters of the patients were compared with 30 healthy persons in the normal control group.</p><p><b>RESULTS</b>(1) In the SQM treated group, after treatment 3 patients got completely remitted (CR), 24 partial remitted (PR), 4 unchanged (NC) and 5 progressively deteriorated (PD), the effective rate being 75.00%; while in the control group, 1 got CR, 19 PR, 9 NC and 7 PD, the effective rate being 55.56%. Comparison of the effective rate between the two groups showed significant difference (P < 0.05). (2) AFP level decreased after treatment in both groups, but the decrement in the treated group was significantly higher than that in the control group (P < 0.01). (3) After treatment, in the treated group, CD3(+), CD4(+), CD4(+)/CD8(+) and NK activity were improved, Karnofsky scores increased and liver function bettered, with these improvements significantly superior to those in the control group (P < 0.01). (4) The improvement in symptoms such as hepatic region pain, fever, weakness, poor appetite and jaundice in the treated group after treatment was also superior to that in the control group (P < 0.01). (5) The 12-month, 18-month and 24-month survival rates were higher and the recurrence rate was lower in the treated group than those in the control group, showing significant difference (P < 0.05).</p><p><b>CONCLUSION</b>Combined therapy with SQM and microwave coagulation could not only kill the tumor and residue tumor cells to prevent recurrence, but also enhance the cellular immunity of organism. It is one of the effective therapies for patients with middle-advanced hepatocarcinoma, who have lost the chance of surgical operation. It could improve clinical symptoms, elevate the quality of life, prolong the survival period of patients, but shows no evident adverse reaction.</p>

Relationship between sCD44v6 expression and TCM differentiation type of gastric carcinoma patients and influence of weitai capsule on the expression / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the relationship of TCM type with serum level of soluble CD44v6 (sCD44v6) and different histologic parameters in gastric carcinoma patients and to observe the influence of Weitai capsule (WTC) on the sCD44v6 expression.</p><p><b>METHODS</b>TCM typing and sCD44v6 expression were determined in all the enrolled patients (30 in the control and 32 in the trial group) before operation, and 3-4 courses of chemotherapy was applied to them from 3-4 weeks after operation. To the patients of trial group, oral administration of WTC was given additionally with 4 capsules, 3 times a day for consecutive 3 months.</p><p><b>RESULTS</b>sCD44v6 was significantly positive correlated with the degree of cancer cell differentiation, infiltration and lymph node metastasis; (2) Level of sCD44v6 was the highest in patients of blood stasis type, as compared with that in the patients of Pi-deficiency type or of damp-heat type, the difference was significant; (3) After ending treatment, level of sCD44v6 in the trial group was significantly lower than that in the control group.</p><p><b>CONCLUSION</b>(1) Serum level of sCD44v6 could be taken as the criterion for evaluating the development and prognosis of gastric cancer, as well as the therapeutic target for anti-metastasis treatment; (2) Serum level of sCD44v6 is related to some extent with TCM type of blood stasis and Pi-deficiency; (3) WTC combined with chemotherapy could further inhibit the expression of serum sCD44v6 in gastric carcinoma patients.</p>

Effects of tumor suppressing gene TIP30/CC3 on the growth of tumor cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To introduce the newly found gene TIP30/CC3 into a hepatoma cell line PLC/PRF/5 and select the stable expression clones. The growth and cell cycles were studied with the clones stably expressing TIP30/CC3 or anti-TIP30/CC3, and the effects of TIP30/CC3 gene on hepatoma cells were analyzed.</p><p><b>METHODS</b>The internal expression of TIP30/CC3 protein was detected with Western blot, then TIP30/CC3 or anti-TIP30/CC3 cDNA was subcloned into a constitutive vector pcDNA3 followed by transfection into PLC/PRF/5. Stable expression clones were selected. The cell growth curve was made and cell cycles detected using flow cytometry. To confirm the results in vitro, stable-expressing cells were implanted subcutaneously into nude mice and time of tumor formation recorded and tumor volume measured.</p><p><b>RESULTS</b>PLC-anti-TIP30 grew faster than the others. Three days after transfection, live cells of PLC-anti-TIP30 were 14.0*10(4), in comparison with the control PLC-DNA3 and PLC/PRF/5, the differences were statistically significant. Live cells of PLC-TIP30 were 4.9*10(4), significantly less than the two control groups. Six days after transfection, live cells of PLC-anti-TIP30 were 25.0*10(4), significantly more than the controls PLC-DNA3 and PLC/PRF/5. Live cells of PLC-TIP30 were 12.4*10(4), significantly less than the two control groups. Cell cycle analysis showed that PLC-anti-TIP30 proliferated faster, 22.4% cells were in G0/G1 (gap) phases and 58.6% cells in S (DNA synthesis) phase. The growth of the PLC-anti-TIP30 cell was retarded and many cells were arrested from G1 to S phases. Cells in G0/G1 and S phase were 44.2% and 33.3% respectively. Furthermore, the average time of tumor formation was shorter in anti-TIP30 group and longer in TIP30/CC3 group, and times were 6.0 d (with control groups) and 15.6 d (with control groups) respectively. Tumors in the nude mice grew faster in PLC-anti-TIP30 group and slower in PLC-TIP30 group.</p><p><b>CONCLUSION</b>Tumor suppressor gene TIP30/CC3 can inhibit the proliferation of tumor cells and interfere in its cell cycles. It can be used as a valuable tool for hepatoma biotherapy including gene therapy.</p>

Relapse or disease-free survival rate prediction value of TIP30 protein expression in NSCLC / 中国癌症杂志

Background and Purpose:TIP30 is a newly found tumor suppressing protein that has low level expression in many kinds of tumor cell lines,and it inhibits the growth of tumor cells of different origin.In this article,we want to probe into the value of a newly found tumor suppressor gene TIP30 as a molecular marker for the prediction of relapse or metastasis of lung cancer patients.Methods:In our present study,immunohistochemical analyses of a retrospective database of pathologic specimens were used to demonstrate the expression of TIP30 protein in NSCLC.Results:The low expression of TIP30 protein in NSCLC tumor tissue was statistically significant in the clinical stage,relapse or metastasis or 5 year disease-free survival rate,whereas low levels of TIP30 expression did not relate to histologic type and histologic differentiation.Conclusions:TIP30 protein may be used as a molecular marker to identify and predict the relapse or metastasis of NSCLC,and may provide a new clue for the clinical doctor to evaluate the prognosis of patients with NSCLC.

Relationship between cell apoptosis and dephosphorylated RB protein in human breast cancer / 中国癌症杂志

Purpose:To investigate the relationship between cell apoptosis and dephosphorylated RB protein in human breast cancer. Methods:In our work,human breast cell lines (MCF-7/S,the chemosensitive cell line and MCF-7/ADR,the chemoresistent cell line)were evaluated. Chemosensitivity of two cell lines was evaluated by the MTT colorimetric assay;the expressive levels of dephosphorylated RB protein were detected with immunocytochemistry. Apoptosis rates were determined by flow cytometry(FCM). Results:ADR inhibited proliferation of chemosensitive cell line MCF-7/S ,the 50% inhibition concentration (IC 50 ) was 0.128 ?g/ml;And IC 50 of MCF-7/ADR was 10.89 ?g/ml. The chemotherapeutic sensitivity of MCF-7/S was more than that of MCF-7/ADR by 86 times . Before treatment with ADR,phosphorylated RB protein was positive in two cell lines,but dephosphorylated RB protein was negative;After treatment of different concentration ADR,when the concentration of ADR was increased,expression of dephosphorylated RB protein elevated accordingly in MCF-7/S,but no significant change in MCF-7/ADR. Apoptosis and cell cycle was detected by FCM assays shows ADR induced apoptosis of MCF-7/S more than MCF-7/ADR(P0.05).